Avacincaptad pegol continues to show promise in slowing the growth rate of geographic atrophy (GA), said Donald J. D’Amico, MD. Speaking on Friday at the Retina Subspecialty Day’s “Late-Breaking Developments, Part 1” session (Ret10V), he presented 18-month results from the GATHER1 study, updating 12-month results recently published in Ophthalmology.1
Rationale for use. Avacincaptad pegol (Zimura, Iveric bio) inhibits complement C5, a component of the complement cascade that plays a role in cell death. Researchers have hypothesized that the drug “may have the potential to slow down the progression of retinal cell degeneration and achieve therapeutic benefit in GA” secondary to age-related macular degeneration (AMD).1
Study design. This phase 2/3 trial consisted of two parts: In part 1, patients were randomized in a 1:1:1 ratio to 1mg Zimura (n = 26), 2 mg Zimura (n = 25), and sham (n = 26). In part 2, they were randomized in a 1:2:2 ratio to 2 mg Zimura (n = 42), 4 mg Zimura (n = 83), and sham (n = 84).
Study results. Both the 2- and 4-mg doses of the active drug met their primary efficacy endpoints. At 12 months, those who received 2- and 4-mg doses of Zimura, respectively, experienced 27% and 28% less growth in GA than did those who received sham treatments. At 18 months, that differential had increased to 28% and 30%, respectively, for the 2- and 4-mg doses of Zimura (vs. sham), Dr. D’Amico .
Safety analysis. No adverse events or cases of inflammation were reported through 18 months, Dr. D’Amico said. However, choroidal neovascularization was observed in the study eyes of two patients who received 1 mg of Zimura (7.7%), eight who received 2 mg (11.9%), and 13 who received 4 mg (15.7%), as well as in three patients (2.7%) in the sham group. In the virtual meeting’s chat box, several attendees expressed concern with this finding, noting that it needs to be studied further.
Continuing investigation. The confirmatory clinical trial, GATHER2, is currently enrolling patients, Dr. D’Amico noted. Participants in GATHER2 will be randomized to receive either Zimura 2 mg or sham. —Jean Shaw
1 Jaffe GJ et al. Ophthalmology. Published online Sept. 1, 2020.
Watch the presentations from Retina Subspecialty Day. If you are registered for AAO 2020 Virtual, you have access to the archived presentations on the virtual meeting platform until Feb. 15, 2021. Log in to the virtual meeting platform: Next, from the Lobby screen, select “Sessions” from the top navigation; click “Agenda” from the drop-down menu; and click on the “Friday” tab.
Financial disclosures. Dr. D’Amico: Alcon: C; Iveric bio: C,O.
Disclosure key. C = Consultant/Advisor; E = Employee; L = Speakers bureau; O = Equity owner; P = Patents/Royalty; S = Grant support.
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